Heterospecific CD4 help to rescue CD8 T cell killers.
Help from CD4 T cells may be required for optimal generation and maintenance of memory CD8 T cells and also for optimal Ag reactivation. We examined whether the helper cell and the CD8 killer cell need to have the same Ag specificity for help to be effective during interactions of memory T cells with mature APC. This is important because virus and tumor Ag-specific CD4 T cell responses are selectively impaired in several chronic viral infections and malignancies. We performed studies in vitro and in vivo and found that functional memory CD4 T cells generated from a distinct antigenic source (heterospecific helpers) could provide direct and effective help to memory CD8 T cells. Functional heterospecific memory CD4 T cells could also rescue secondary CD8 T cell responses in an experimental tumor model in which homospecific CD4 help was impaired. This could provide a rationale for immunotherapy strategies designed to bypass impaired homospecific help.
de Goër de Herve
Marie-Ghislaine
MG
Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre, France.
Cariou
Anne
A
Simonetta
Federico
F
Taoufik
Yassine
Y
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000502:physiology* / Q000627:therapeutic use; D005260:Female; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000502:physiology* / Q000627:therapeutic use; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000637:transplantation*; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes